Synthetic Cannabigerol Quinone Analogs and Pharmaceutical Compositions Containing Same for Treating Neurological Disorders

Abstract

Cannabinoid analogs may exhibit anti-inflammatory properties such as by inhibition of cannabinoid type 2 (CB2) receptors. Pharmaceutical compositions comprising the cannabinoid analogs may be used to treat various diseases and conditions in mammals, including pain, anxiety, addiction, epilepsy, depression, or Alzheimer's disease.

What is claimed is: 
     
         1 . A synthetic cannabinoid analog having a structure of Formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is selected from the group consisting of aryl, alkenyl, alkynyl, alkoxycarbonyl, alkylamino, arylamino, alkenylamino, and alkynylamino; or R 1  represents a bond between two molecules of Formula (I) forming a dimer; 
         R 2  is selected from the group consisting of H, OH, protected hydroxyl, alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein the alkyl, alkenyl, alkynyl or acyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR A R B , —S-alkyl, —SO-alkyl, —SO 2 -alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein R A  and R B  are each independently selected from hydrogen and C 1-4  alkyl; wherein the aryl or heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, —COOH, —C(O)—C 1-4  alkyl, —C(O)O—C 1-4  alkyl, NR C R D , —S-alkyl, —SO-alkyl and —SO 2 -alkyl; wherein R C  and R D  are each independently selected from hydrogen and C 1-4  alkyl; and 
         R 3  is selected from the group consisting of H, alkyl, acyl, —SO 2 -alkyl, —SO 2 -aryl and —SO 2 -heteroaryl; wherein the alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR E R F , —S-alkyl, —SO-alkyl, —SO 2 -alkyl, aryl and heteroaryl; and wherein R E  and R F  are each independently selected from hydrogen and C 1-4  alkyl; wherein the aryl or heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR G R H , —S-alkyl, —SO-alkyl and —SO 2 -alkyl; wherein R G  and R H  are each independently selected from hydrogen and C 1-4  alkyl;
 or a pharmaceutically acceptable salt or ester thereof. 
 
       
     
     
         2 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable vehicle therefor. 
     
     
         3 . A pharmaceutical composition of  claim 2 , wherein the pharmaceutically acceptable vehicle is selected from the group consisting of a capsule, tablet, syrup, lozenge, inhaler, chewable gum, nasal spray, transdermal patch, liquid, transmucosal vehicle, hydrogel, nanosome, liposome, noisome, nanoparticle, nanosphere, microsphere, microparticle, microemulsion, nanosuspension, and micelle. 
     
     
         4 . A method of treating a cancer, tumor, addiction, epilepsy, anxiety, or depression comprising administering to an individual in need thereof a pharmaceutical composition of  claim 3 . 
     
     
         5 . A synthetic cannabinoid analog having a structure of Formula (II): 
       
         
           
           
               
               
           
         
         wherein R 2  is selected from the group consisting of H, OH, protected hydroxyl, alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein the alkyl, alkenyl, alkynyl or acyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR A R B , —S-alkyl, —SO-alkyl, —SO 2 -alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein R A  and R B  are each independently selected from hydrogen and C 1-4  alkyl; wherein the aryl or heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, —COH, —C(O)C 1-4  alkyl, —C(O)O—C 1-4  alkyl, NR C R D , —S-alkyl, —SO-alkyl and —SO 2 -alkyl; wherein R C  and R D  are each independently selected from hydrogen and C 1-4  alkyl; 
         R 3  is selected from the group consisting of H, alkyl, acyl, —SO 2 -alkyl, —SO 2 -aryl and —SO 2 -heteroaryl; wherein the alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR E R F , —S-alkyl, —SO-alkyl, —SO 2 -alkyl, aryl and heteroaryl; and wherein R E  and R F  are each independently selected from hydrogen and C 1-4  alkyl; wherein the aryl or heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR G R H , —S-alkyl, —SO-alkyl and —SO 2 -alkyl; wherein R G  and R H  are each independently selected from hydrogen and C 1-4  alkyl; and 
         R 4  is optionally substituted alkyl;
 or a pharmaceutically acceptable salt or ester thereof. 
 
       
     
     
         6 . A pharmaceutical composition comprising a compound of  claim 5  and a pharmaceutically acceptable vehicle therefor. 
     
     
         7 . A pharmaceutical composition of  claim 6 , wherein the pharmaceutically acceptable vehicle is selected from the group consisting of a capsule, tablet, syrup, lozenge, inhaler, chewable gum, nasal spray, transdermal patch, liquid, transmucosal vehicle, hydrogel, nanosome, liposome, noisome, nanoparticle, nanosphere, microsphere, microparticle, microemulsion, nanosuspension, and micelle. 
     
     
         8 . A method of treating anxiety, addiction, or depression comprising administering to an individual in need thereof a pharmaceutical composition of  claim 7 . 
     
     
         9 . A method of treating Alzheimer's disease comprising administering to an individual in need thereof a pharmaceutical composition of  claim 7 . 
     
     
         10 . A synthetic cannabinoid analog having a structure selected from the group consisting of: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         11 . A pharmaceutical composition comprising a compound of  claim 10  and a pharmaceutically acceptable vehicle therefor. 
     
     
         12 . A method of treating anxiety, addiction, or depression comprising administering to an individual in need thereof a pharmaceutical composition of  claim 11 . 
     
     
         13 . A method of treating Alzheimer's disease comprising administering to an individual in need thereof a pharmaceutical composition of  claim 11 .